Format

Send to:

Choose Destination

KCNH2 potassium voltage-gated channel subfamily H member 2 [ Homo sapiens (human) ]

Gene ID: 3757, updated on 29-May-2016
Official Symbol
KCNH2provided by HGNC
Official Full Name
potassium voltage-gated channel subfamily H member 2provided by HGNC
Primary source
HGNC:HGNC:6251
See related
Ensembl:ENSG00000055118 HPRD:01069; MIM:152427; Vega:OTTHUMG00000158341
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
ERG1; HERG; LQT2; SQT1; ERG-1; H-ERG; HERG1; Kv11.1
Summary
This gene encodes a voltage-activated potassium channel belonging to the eag family. It shares sequence similarity with the Drosophila ether-a-go-go (eag) gene. Mutations in this gene can cause long QT syndrome type 2 (LQT2). Transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, Jul 2008]
Orthologs
Location:
7q36.1
Exon count:
17
Annotation release Status Assembly Chr Location
107 current GRCh38.p2 (GCF_000001405.28) 7 NC_000007.14 (150944956..150978314, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 7 NC_000007.13 (150642044..150675402, complement)

Chromosome 7 - NC_000007.14Genomic Context describing neighboring genes Neighboring gene transmembrane protein 176B Neighboring gene transmembrane protein 176A Neighboring gene uncharacterized LOC105375567 Neighboring gene amine oxidase, copper containing 1 Neighboring gene nitric oxide synthase 3 Neighboring gene uncharacterized LOC105375568 Neighboring gene autophagy related 9B

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Professional guidelines

Description
Professional guideline
ACMG 2013

The ACMG recommends that laboratories performing clinical sequencing seek and report mutations in KCNH2 that are pathogenic or expected to be pathogenic.

GuidelinePubMed

Associated conditions

Description Tests
Long QT syndrome 2
MedGen: C3150943 OMIM: 613688 GeneReviews: Long QT Syndrome
Compare labs
Short QT syndrome 1
MedGen: C1865020 OMIM: 609620 GeneReviews: Not available
Compare labs

Copy number response

Description
Copy number response
Triplosensitivity

No evidence available (Last evaluated (2016-01-14)

ClinGen Genome Curation Page
Haploinsufficency

Sufficient evidence for dosage pathogenicity (Last evaluated (2016-01-14)

ClinGen Genome Curation PagePubMed

NHGRI GWAS Catalog

Description
Common variants at ten loci influence QT interval duration in the QTGEN Study.
NHGRI GWA Catalog
Common variants at ten loci modulate the QT interval duration in the QTSCD Study.
NHGRI GWA Catalog
Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.
NHGRI GWA Catalog
Genetic variation in SCN10A influences cardiac conduction.
NHGRI GWA Catalog
Impact of ancestry and common genetic variants on QT interval in African Americans.
NHGRI GWA Catalog
Several common variants modulate heart rate, PR interval and QRS duration.
NHGRI GWA Catalog

Protein interactions

Protein Gene Interaction Pubs
Tat tat HIV-1 Tat protein inhibits hERG K(+) currents through the inhibition of hERG protein expression PubMed

Go to the HIV-1, Human Interaction Database

  • Cardiac conduction, organism-specific biosystem (from REACTOME)
    Cardiac conduction, organism-specific biosystemThe normal sequence of contraction of atria and ventricles of the heart require activation of groups of cardiac cells. The mechanism must elicit rapid changes in heart rate and respond to changes in ...
  • Muscle contraction, organism-specific biosystem (from REACTOME)
    Muscle contraction, organism-specific biosystemIn this module, the processes by which calcium binding triggers actin - myosin interactions and force generation in smooth and striated muscle tissues are annotated.
  • Neuronal System, organism-specific biosystem (from REACTOME)
    Neuronal System, organism-specific biosystemThe human brain contains at least 100 billion neurons, each with the ability to influence many other cells. Clearly, highly sophisticated and efficient mechanisms are needed to enable communication a...
  • Phase 3 - rapid repolarisation, organism-specific biosystem (from REACTOME)
    Phase 3 - rapid repolarisation, organism-specific biosystemIn phase 3 (the "rapid repolarisation" phase), the L-type Ca2+ channels close, while the slow delayed rectifier (IKs) K+ channels remain open as more K+ leak channels open. This ensures a net outward...
  • Potassium Channels, organism-specific biosystem (from REACTOME)
    Potassium Channels, organism-specific biosystemPotassium channels are tetrameric ion channels that are widely distributed and are found in all cell types. Potassium channels control resting membrane potential in neurons, contribute to regulation ...
  • SIDS Susceptibility Pathways, organism-specific biosystem (from WikiPathways)
    SIDS Susceptibility Pathways, organism-specific biosystemIn this model, we provide an integrated view of Sudden Infant Death Syndrome (SIDS) at the level of implicated tissues, signaling networks and genetics. The purpose of this model is to serve as an ov...
  • Voltage gated Potassium channels, organism-specific biosystem (from REACTOME)
    Voltage gated Potassium channels, organism-specific biosystemVoltage-gated K+ channels (Kv) determine the excitability of heart, brain and skeletal muscle cells. Kv form octameric channel with alpha subunits that forms the pore of the channel and associated be...
Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Gene Ontology Provided by GOA

Process Evidence Code Pubs
cardiac conduction TAS
Traceable Author Statement
more info
 
cardiac muscle contraction IMP
Inferred from Mutant Phenotype
more info
PubMed 
cellular response to drug IDA
Inferred from Direct Assay
more info
PubMed 
membrane depolarization during action potential IDA
Inferred from Direct Assay
more info
PubMed 
membrane repolarization during action potential IDA
Inferred from Direct Assay
more info
PubMed 
membrane repolarization during cardiac muscle cell action potential IMP
Inferred from Mutant Phenotype
more info
PubMed 
membrane repolarization during ventricular cardiac muscle cell action potential IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of potassium ion export IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of potassium ion transmembrane transport IDA
Inferred from Direct Assay
more info
PubMed 
phosphorelay signal transduction system IEA
Inferred from Electronic Annotation
more info
 
positive regulation of potassium ion transmembrane transport IDA
Inferred from Direct Assay
more info
PubMed 
potassium ion export IDA
Inferred from Direct Assay
more info
PubMed 
potassium ion export across plasma membrane IGI
Inferred from Genetic Interaction
more info
PubMed 
potassium ion homeostasis IDA
Inferred from Direct Assay
more info
PubMed 
potassium ion transmembrane transport IDA
Inferred from Direct Assay
more info
PubMed 
regulation of heart rate by cardiac conduction IMP
Inferred from Mutant Phenotype
more info
PubMed 
regulation of heart rate by hormone TAS
Traceable Author Statement
more info
PubMed 
regulation of membrane potential IDA
Inferred from Direct Assay
more info
PubMed 
regulation of membrane repolarization IDA
Inferred from Direct Assay
more info
PubMed 
regulation of potassium ion transmembrane transport IDA
Inferred from Direct Assay
more info
PubMed 
regulation of ventricular cardiac muscle cell membrane repolarization IMP
Inferred from Mutant Phenotype
more info
PubMed 
signal transduction by protein phosphorylation IEA
Inferred from Electronic Annotation
more info
 
ventricular cardiac muscle cell action potential IMP
Inferred from Mutant Phenotype
more info
PubMed 
Component Evidence Code Pubs
cell surface IDA
Inferred from Direct Assay
more info
PubMed 
perinuclear region of cytoplasm IMP
Inferred from Mutant Phenotype
more info
PubMed 
plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
plasma membrane IMP
Inferred from Mutant Phenotype
more info
PubMed 
plasma membrane TAS
Traceable Author Statement
more info
 
voltage-gated potassium channel complex IDA
Inferred from Direct Assay
more info
PubMed 
voltage-gated potassium channel complex IMP
Inferred from Mutant Phenotype
more info
PubMed 
Preferred Names
potassium voltage-gated channel subfamily H member 2
Names
eag homolog
eag-related protein 1
ether-a-go-go-related gene potassium channel 1
ether-a-go-go-related potassium channel protein
ether-a-go-go-related protein 1
potassium channel, voltage gated eag related subfamily H, member 2
potassium voltage-gated channel, subfamily H (eag-related), member 2
voltage-gated potassium channel subunit Kv11.1

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_008916.1 RefSeqGene

    Range
    4613..37971
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_288

mRNA and Protein(s)

  1. NM_000238.3NP_000229.1  potassium voltage-gated channel subfamily H member 2 isoform a

    See identical proteins and their annotated locations for NP_000229.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longest isoform (a).
    Source sequence(s)
    AF363636, BM674996, DQ525913, U04270
    Consensus CDS
    CCDS5910.1
    UniProtKB/Swiss-Prot
    Q12809
    UniProtKB/TrEMBL
    A0A090N8Q0, Q15BH2
    Related
    ENSP00000262186, OTTHUMP00000212821, ENST00000262186, OTTHUMT00000350741
    Conserved Domains (6) summary
    COG0664
    Location:736856
    Crp; cAMP-binding domain of CRP or a regulatory subunit of cAMP-dependent protein kinases [Signal transduction mechanisms]
    cd00038
    Location:742853
    CAP_ED; effector domain of the CAP family of transcription factors; members include CAP (or cAMP receptor protein (CRP)), which binds cAMP, FNR (fumarate and nitrate reduction), which uses an iron-sulfur cluster to sense oxygen) and CooA, a heme containing CO ...
    cd00130
    Location:41132
    PAS; PAS domain; PAS motifs appear in archaea, eubacteria and eukarya. Probably the most surprising identification of a PAS domain was that in EAG-like K+-channels. PAS domains have been found to bind ligands, and to act as sensors for light and oxygen in ...
    pfam00520
    Location:454659
    Ion_trans; Ion transport protein
    pfam07885
    Location:611660
    Ion_trans_2; Ion channel
    pfam13426
    Location:29130
    PAS_9; PAS domain
  2. NM_001204798.1NP_001191727.1  potassium voltage-gated channel subfamily H member 2 isoform d

    See identical proteins and their annotated locations for NP_001191727.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) differs in the 5' and 3' UTRs and 5' and 3' coding regions compared to variant 1, resulting in a shorter isoform (d) with different N- and C-termini compared to isoform a.
    Source sequence(s)
    AJ609614, BC001914, BG683210, BQ478289
    UniProtKB/Swiss-Prot
    Q12809
    Conserved Domains (3) summary
    cd00038
    Location:402462
    CAP_ED; effector domain of the CAP family of transcription factors; members include CAP (or cAMP receptor protein (CRP)), which binds cAMP, FNR (fumarate and nitrate reduction), which uses an iron-sulfur cluster to sense oxygen) and CooA, a heme containing CO ...
    pfam00520
    Location:114319
    Ion_trans; Ion transport protein
    pfam07885
    Location:271320
    Ion_trans_2; Ion channel
  3. NM_172056.2NP_742053.1  potassium voltage-gated channel subfamily H member 2 isoform b

    See identical proteins and their annotated locations for NP_742053.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2), also known as HERG-USO, differs in the 3' UTR and 3' coding region compared to variant 1, resulting in a shorter isoform (b) with a different C-terminus compared to isoform a.
    Source sequence(s)
    AB044806, BC001914, BQ478289, DQ525913
    UniProtKB/Swiss-Prot
    Q12809
    UniProtKB/TrEMBL
    A0A090N7W1, Q15BH2
    Related
    ENSP00000387657, ENST00000430723
    Conserved Domains (5) summary
    cd00038
    Location:742802
    CAP_ED; effector domain of the CAP family of transcription factors; members include CAP (or cAMP receptor protein (CRP)), which binds cAMP, FNR (fumarate and nitrate reduction), which uses an iron-sulfur cluster to sense oxygen) and CooA, a heme containing CO ...
    cd00130
    Location:41132
    PAS; PAS domain; PAS motifs appear in archaea, eubacteria and eukarya. Probably the most surprising identification of a PAS domain was that in EAG-like K+-channels. PAS domains have been found to bind ligands, and to act as sensors for light and oxygen in ...
    pfam00520
    Location:454659
    Ion_trans; Ion transport protein
    pfam07885
    Location:611660
    Ion_trans_2; Ion channel
    pfam13426
    Location:29130
    PAS_9; PAS domain
  4. NM_172057.2NP_742054.1  potassium voltage-gated channel subfamily H member 2 isoform c

    See identical proteins and their annotated locations for NP_742054.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3), also known as HERG1b, differs in the 5' UTR and 5' coding region compared to variant 1, resulting in a shorter isoform (c) with a different N-terminus compared to isoform a.
    Source sequence(s)
    AJ512214, BG683210, BM674996, U04270
    Consensus CDS
    CCDS5911.1
    UniProtKB/Swiss-Prot
    Q12809
    UniProtKB/TrEMBL
    A0A090N7X5
    Related
    ENSP00000328531, OTTHUMP00000212824, ENST00000330883, OTTHUMT00000350744
    Conserved Domains (4) summary
    COG0664
    Location:396516
    Crp; cAMP-binding domain of CRP or a regulatory subunit of cAMP-dependent protein kinases [Signal transduction mechanisms]
    cd00038
    Location:402513
    CAP_ED; effector domain of the CAP family of transcription factors; members include CAP (or cAMP receptor protein (CRP)), which binds cAMP, FNR (fumarate and nitrate reduction), which uses an iron-sulfur cluster to sense oxygen) and CooA, a heme containing CO ...
    pfam00520
    Location:114319
    Ion_trans; Ion transport protein
    pfam07885
    Location:271320
    Ion_trans_2; Ion channel

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 107 details...

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p2 Primary Assembly

Genomic

  1. NC_000007.14 Reference GRCh38.p2 Primary Assembly

    Range
    150944956..150978314 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011516185.1XP_011514487.1  

    Conserved Domains (4) summary
    COG0664
    Location:636756
    Crp; cAMP-binding domain of CRP or a regulatory subunit of cAMP-dependent protein kinases [Signal transduction mechanisms]
    cd00038
    Location:642753
    CAP_ED; effector domain of the CAP family of transcription factors; members include CAP (or cAMP receptor protein (CRP)), which binds cAMP, FNR (fumarate and nitrate reduction), which uses an iron-sulfur cluster to sense oxygen) and CooA, a heme containing CO ...
    pfam00520
    Location:354559
    Ion_trans; Ion transport protein
    pfam07885
    Location:511560
    Ion_trans_2; Ion channel
  2. XM_011516186.1XP_011514488.1  

    Conserved Domains (6) summary
    COG0664
    Location:736856
    Crp; cAMP-binding domain of CRP or a regulatory subunit of cAMP-dependent protein kinases [Signal transduction mechanisms]
    cd00038
    Location:742853
    CAP_ED; effector domain of the CAP family of transcription factors; members include CAP (or cAMP receptor protein (CRP)), which binds cAMP, FNR (fumarate and nitrate reduction), which uses an iron-sulfur cluster to sense oxygen) and CooA, a heme containing CO ...
    cd00130
    Location:41132
    PAS; PAS domain; PAS motifs appear in archaea, eubacteria and eukarya. Probably the most surprising identification of a PAS domain was that in EAG-like K+-channels. PAS domains have been found to bind ligands, and to act as sensors for light and oxygen in ...
    pfam00520
    Location:454659
    Ion_trans; Ion transport protein
    pfam07885
    Location:611660
    Ion_trans_2; Ion channel
    pfam13426
    Location:29130
    PAS_9; PAS domain

Alternate CHM1_1.1

Genomic

  1. NC_018918.2 Alternate CHM1_1.1

    Range
    150650401..150683838 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)